Hepatitis B is a disease which is induced by a hepatitis B virus (hereinafter, referred to as "HBV") and includes immunologically and clinically very serious problems, but there has never been found any effective therapeutic method therefor. This disease has been observed worldwidely, particularly in Asia and Africa areas.
Against the disease, prophylactic method has mostly been studied. Suitable prophylaxis is a method of applying a vaccine comprising as an effective ingredient HBs antigen to persons who are afraid to be infected by HBV. A vaccine has already been in practical use, which is prepared by highly purifying an HBs antigen obtained from a blood plasma of latent virus carriers who are usually called as merely "carrier", and inactivating the purified HBs antigen.
However, the blood-origin vaccine is obtained from blood plasma of HBs antigen-positive persons, and hence, it has various problems for the preparation thereof, such as necessity of safety test in chimpanzee in order to prove no remaining of infectious factors such as HBV or any other blood-origin viruses in the preparation; and difficulty to get sufficient chimpanzees for the test.
In order to eliminate such problems, many researchers have been studied on technique for obtaining a large amount of the HBs antigen by introducing an HBV DNA encoding the HBs antigen protein into Escherichia coli or an yeast by means of a DNA recombination technique and then expressing the HBs antigen by the transformant microorganisms thus obtained. Recently, the expression of HBs antigen with these recombinant organisms has been succeeded. Particularly, the production of HBs antigen with a recombinant yeast has been accomplished in an industrial scale, and it has been tried to purify the HBs antigen thus obtained and to prepare a hepatitis B vaccine preparation therefrom. In order to use practically the recombinant-origin HBs antigen, there is still a problem that the HBs antigen produced by the recombinant organisms must be highly purified in a so high degree suitable for the desired vaccine stock or for diagnosis.